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R. Jungwirth - One of the best experts on this subject based on the ideXlab platform.
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In vitro activity and stability against novel beta-lactamases of investigational beta-lactams (cefepime, cefpirome, flomoxef, SCE 2787 and Piperacillin Plus Tazobactam) in comparison with established compounds (cefotaxime, latamoxef and Piperacillin)
Infection, 1991Co-Authors: A. Bauernfeind, S. Schweighart, E. Eberlein, R. JungwirthAbstract:Die Perspektiven für eine Verbesserung der antiinfektiösen Therapie mit Hilfe neuer Betalaktamantibiotika (Flomoxef, SCE 2787, Cefpirom, Cefepim, Piperacillin Plus Tazobactam) im Vergleich mit Cefotaxim und Latamoxef wurden durch Vergleich ihrer in vitro Aktivitäten gegenüber 1119 Isolaten aus 83 Spezies analysiert. Escherichia coli, Klebsiella spp., Enterobacter sakazakii, Proteus spp. und Shigella spp. erwiesen sich als etwa gleich sensitiv gegenüber allen Cephalosporinen (MHK_90: 0,06 und 0,5 mg/l) während die MHK_90 für Piperacillin Plus Tazobactam zwischen 2 und 16 mg/l lagen. Enterobacter cloacae, Enterobacter aerogenes und Serratia spp. waren am empfindlichsten gegenüber SCE 2787, Cefpirom und Cefepim (MHK_90: 0,06–2 mg/l), es folgten Latamoxef, Cefotaxim, Flomoxef und Piperacillin Plus Tazobactam. Bei Citrobacter spp. Providencia spp. und Yersinia enterocolitica lagen die MHK_90 Werte zwischen 0,06 und 0,5 mg/l, Flomoxef war gegen diese Spezies 2 bis 16 mal weniger aktiv, jedoch aktiver als Piperacillin Plus Tazobactam (MHK_90: 2–8 mg/l). Gegen Morganella morganii und Hafnia alvei waren Cefepim, Cefpirom und Latamoxef die wirksamsten Substanzen (MHK_90 zwischen 0,13 und 0,5 mg/l) während Cefotaxim (MHK_90: 8 mg/l) und Piperacillin Plus Tazobactam (MHK_90: 8 bis > 64 mg/l) die niedrigste Aktivität aufwiesen. Gegen nichtfermentierende Bakterien (13 Spezies) zeigten SCE 2787, Cefepim und Cefpirom die höchste Aktivität (MHK_90: 0,5–16 mg/l). Hier waren die Oxacepheme am wenigsten wirksam. Cefepim war unter den hier verglichenen Betalaktamen das aktivste gegenüber Pseudomonas aeruginosa (MHK_90 16 mg/l). Haemophilus spp., Neisseria gonorrhoeae und Bordetella pertussis waren am empfindlichsten gegenüber Cefotaxim (MHK_90: 0,03–0,06 mg/l). Gegenüber allen grampositiven Kokken waren alle einbezogenen Substanzen deutlich stärker aktiv als Latamoxef (MHK_90 gegenüber Staphylokokken 8–64 mg/l, Streptokokken, außer Enterkokken, 4–8 mg/l). Unter den Methicillin-sensitiven Staphylokokken waren die penicillinasebildenden Staphylococcus aureus Stämme am empfindlichsten gegen Flomoxef, die Isolate der übrigen Staphylokokken Spezies waren etwa gleich sensitiv gegenüber allen Substanzen. Streptokokken (ohne Enterokokken) hatten MHK_90-Werte zwischen 0,03 und 0,5 mg/l. Streptococcus pneumoniae Isolate mit MHK-Werte für Penicillin über 1 mg/l waren zwischen 16 und 64 mal weniger empfindlich (MHK_90: 0,5 bis 4 mg/l) gegenüber anderen Betalaktamen als penicillinempfindliche Pneumokokken (MHK_90: 0,03 bis 0,13). Gegenüber Isolaten anaerober Spezies waren Flomoxef und Piperacillin Plus Tazobactam die aktivsten Substanzen. Das Oxacephem Flomoxef war die stabilste Verbindung gegenüber neuen Betalaktamasen mit erweitertem Breitsprektrum (TEM-3 bis TEM-7, SHV-2 bis SHV-5, CMY-1, CTX-M-1) gefolgt von Latamoxef. Beide Oxacephamycine werden jedoch von Cephamycinasen hydrolysiert. Weitgehend cephamycinasefest sind SCE 2787, Cefepim und Cefpirom. Somit konnten Möglichkeiten antibiotischer Therapie mithilfe parenteraler Betalaktame verbessert werden sowohl durch Derivate eingeführter Substanzen als auch durch deren Kombination mit Betalaktamaseinhibitoren (Piperacillin Plus Tazobactam): Die Latamoxef-Lücke gegenüber grampositiven Kokken ließ sich mit dem Flomoxef schließen und die Aktivität gegenüber Streptokokken um das 16- bis 32fache erhöhen. Die Cefotaxim-Derivate (SCE 2787, Cefepim, Cefpirom) verfügen bei vielen Spezies über erhöhte antibakterielle Aktivität gegenüber der Ausgangssubstanz (insbesondere gegenüber Spezies mit chromosomalen Betalaktamasen wie Enterobacter spp., Serratia spp., H. alvei, M. morganii und nichtfermentierende Bakterien). Tazobactam schützt das Piperacillin vor plasmidischen Betalaktamasen jedoch nicht in dem Ausmaß wie das durch die strukturelle Veränderung der Aminothiazolmethoximino-cephalosporinstruktur (SCE 2787, Cefepim, Cefpirom) oder insbesondere durch Flomoxef erreicht werden konnte. The therapeutic perspectives of flomoxef, SCE 2787, cefpirome, cefepime, latamoxef, cefotaxime and of Piperacillin Plus Tazobactam were comparatively evaluated by their in vitro activity against 1119 clinical isolates of 83 bacterial species. Escherichia coli, Klebsiella spp. Enterobacter sakazakii, Proteus spp. and Shigella spp. were about equally susceptible to the cephalosporins (MIC_90: 0.06 to 0.5 mg/l), while the MIC_90 for Piperacillin Plus Tazobactam was between 2 and 16 mg/l. Enterobacter cloacae, Enterobacter aerogenes and Serratia spp. were most susceptible to SCE 2787, cefpirome and cefepime (MIC_90: 0.06 to 2 mg/l) followed by latamoxef, cefotaxime, flomoxef and Piperacillin Plus Tazobactam. For Citrobacter spp., Providencia spp. and Yersinia enterocolitica MIC_90 were between 0.06 and 0.5 mg/l. Flomoxef was between 2 to 4 log_2 less active against these species but more active than Piperacillin Plus Tazobactam (MIC_90: 2 and 8 mg/l). Morganella morganii and Hafnia alvei were most susceptible to cefepime, cefpirome and latamoxef (MIC_90: 0.13 to 0.5 mg/l) while cefotaxime (MIC_90: 8 mg/l) and Piperacillin Plus Tazobactam (MIC_90: 8 and > 64 mg/l) were the least active compounds. SCE 2787, cefepime and cefpirome were the most potent beta-lactams against the majority of the 13 species of non-fermentative bacilli (NFB) investigated (MIC_90: 0.5 to 16 mg/l). The oxacephems were the least active compounds against NFB. Cefepime was the most active of the compounds included against Pseudomonas aeruginosa (MIC_90: 16 mg/l). Haemophilus spp., Neisseria gonorrhoeae and Bordetella pertussis were most susceptible to cefotaxime (MIC_90: 0.03 to 0.06 mg/l). Latamoxef had the lowest activity of all compounds against gram-positive cocci. Flomoxef was the most active compound against penicillinase producing Staphylococcus aureus and about equally active as the other betalactams against methicillin susceptible staphylococci of other staphylococcal species. Non-enterococcal streptococci had MIC_90 between 0.03 und 0.5 mg/l for all. Streptococcus pneumoniae with MICs for penicillin equal to or above 1 mg/l were between 16 and 64 times less susceptible (MIC_90: between 0.5 and 4 mg/l) than penicillin-susceptible organisms (MIC_90: between 0.03 and 0.13 mg/l). Flomoxef and Piperacillin Plus Tazobactam were the most active of the compounds against anaerobic organisms. The oxacephem flomoxef was the most stable of the compounds included against novel extended broad spectrum beta-lactamases (TEM-3 to TEM-7, SHV-2 to SHV 5, CMY-1, CTX-M-1) followed by latamoxef. However, both oxacephamycins are hydrolysed by cephamycinases while SCE 2787, cefepime and cefpirome are stable against cephamycinases. Progress in antibacterial activity of parenteral cephalosporins was achieved both by structural modifications (of latamoxef or cefotaxime) and combination of Piperacillin with taxobactam. Flomoxef in comparison with latamoxef extended its spectrum to include staphylococci and increased activity against non-enterococcal streptococci 16 to 32 times. The various structural modifications of cefotaxime at position 3 of the cephalosporin ring improved the antibacterial profile of SCE 2787, cefepime and cefpirome in very much the same way (enhanced activity mainly against organisms producing chromosomal cephalosporinases, e. g. Enterobacter spp., Serratia spp., H. alvei, M. morganii and non-fermentative bacilli). Tazobactam protects Piperacillin against plasmidic beta-lactamases, however, this was achieved to an even higher extent by the structural modifications of aminothiazole-methoximino cephalosporins (SCE 2787, cefepime and cefpirome) and in particular of flomoxef.
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In vitro activity and stability against novel beta-lactamases of investigational beta-lactams (cefepime, cefpirome, flomoxef, SCE2787 and Piperacillin Plus Tazobactam) in comparison with established compounds (cefotaxime, latamoxef and Piperacillin).
Infection, 1991Co-Authors: A. Bauernfeind, S. Schweighart, E. Eberlein, R. JungwirthAbstract:The therapeutic perspectives of flomoxef, SCE 2787, cefpirome, cefepime, latamoxef, cefotaxime and of Piperacillin Plus Tazobactam were comparatively evaluated by their in vitro activity against 1119 clinical isolates of 83 bacterial species. Escherichia coli, Klebsiella spp. Enterobacter sakazakii, Proteus spp. and Shigella spp. were about equally susceptible to the cephalosporins (MIC90: 0.06 to 0.5 mg/l), while the MIC90 for Piperacillin Plus Tazobactam was between 2 and 16 mg/l. Enterobacter cloacae, Enterobacter aerogenes and Serratia spp. were most susceptible to SCE 2787, cefpirome and cefepime (MIC90: 0.06 to 2 mg/l) followed by latamoxef, cefotaxime, flomoxef and Piperacillin Plus Tazobactam. For Citrobacter spp., Providencia spp. and Yersinia enterocolitica MIC90 were between 0.06 and 0.5 mg/l. Flomoxef was between 2 to 4 log2 less active against these species but more active than Piperacillin Plus Tazobactam (MIC90: 2 and 8 mg/l). Morganella morganii and Hafnia alvei were most susceptible to cefepime, cefpirome and latamoxef (MIC90: 0.13 to 0.5 mg/l) while cefotaxime (MIC90: 8 mg/l) and Piperacillin Plus Tazobactam (MIC90: 8 and greater than 64 mg/l) were the least active compounds. SCE 2787, cefepime and cefpirome were the most potent beta-lactams against the majority of the 13 species of non-fermentative bacilli (NFB) investigated (MIC90: 0.5 to 16 mg/l). The oxacephems were the least active compounds against NFB. Cefepime was the most active of the compounds included against Pseudomonas aeruginosa (MIC90: 16 mg/l). Haemophilus spp., Neisseria gonorrhoeae and Bordetella pertussis were most susceptible to cefotaxime (MIC90: 0.03 to 0.06 mg/l). Latamoxef had the lowest activity of all compounds against gram-positive cocci. Flomoxef was the most active compound against penicillinase producing Staphylococcus aureus and about equally active as the other betalactams against methicillin susceptible staphylococci of other staphylococcal species.(ABSTRACT TRUNCATED AT 250 WORDS)
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in vitro activity and stability against novel beta lactamases of investigational beta lactams cefepime cefpirome flomoxef sce 2787 and Piperacillin Plus Tazobactam in comparison with established compounds cefotaxime latamoxef and Piperacillin
Infection, 1991Co-Authors: A. Bauernfeind, S. Schweighart, E. Eberlein, R. JungwirthAbstract:The therapeutic perspectives of flomoxef, SCE 2787, cefpirome, cefepime, latamoxef, cefotaxime and of Piperacillin Plus Tazobactam were comparatively evaluated by theirin vitro activity against 1119 clinical isolates of 83 bacterial species.Escherichia coli, Klebsiella spp.Enterobacter sakazakii, Proteus spp. andShigella spp. were about equally susceptible to the cephalosporins (MIC90: 0.06 to 0.5 mg/l), while the MIC90 for Piperacillin Plus Tazobactam was between 2 and 16 mg/l.Enterobacter cloacae, Enterobacter aerogenes andSerratia spp. were most susceptible to SCE 2787, cefpirome and cefepime (MIC90: 0.06 to 2 mg/l) followed by latamoxef, cefotaxime, flomoxef and Piperacillin Plus Tazobactam. ForCitrobacter spp.,Providencia spp. andYersinia enterocolitica MIC90 were between 0.06 and 0.5 mg/l. Flomoxef was between 2 to 4 log2 less active against these species but more active than Piperacillin Plus Tazobactam (MIC90: 2 and 8 mg/l).Morganella morganii andHafnia alvei were most susceptible to cefepime, cefpirome and latamoxef (MIC90: 0.13 to 0.5 mg/l) while cefotaxime (MIC90: 8 mg/l) and Piperacillin Plus Tazobactam (MIC90: 8 and > 64 mg/l) were the least active compounds. SCE 2787, cefepime and cefpirome were the most potent beta-lactams against the majority of the 13 species of non-fermentative bacilli (NFB) investigated (MIC90: 0.5 to 16 mg/l). The oxacephems were the least active compounds against NFB. Cefepime was the most active of the compounds included againstPseudomonas aeruginosa (MIC90: 16 mg/l).Haemophilus spp.,Neisseria gonorrhoeae andBordetella pertussis were most susceptible to cefotaxime (MIC90: 0.03 to 0.06 mg/l). Latamoxef had the lowest activity of all compounds against gram-positive cocci. Flomoxef was the most active compound against penicillinase producingStaphylococcus aureus and about equally active as the other betalactams against methicillin susceptible staphylococci of other staphylococcal species. Non-enterococcal streptococci had MIC90 between 0.03 und 0.5 mg/l for all.Streptococcus pneumoniae with MICs for penicillin equal to or above 1 mg/l were between 16 and 64 times less susceptible (MIC90: between 0.5 and 4 mg/l) than penicillin-susceptible organisms (MIC90: between 0.03 and 0.13 mg/l). Flomoxef and Piperacillin Plus Tazobactam were the most active of the compounds against anaerobic organisms. The oxacephem flomoxef was the most stable of the compounds included against novel extended broad spectrum beta-lactamases (TEM-3 to TEM-7, SHV-2 to SHV 5, CMY-1, CTX-M-1) followed by latamoxef. However, both oxacephamycins are hydrolysed by cephamycinases while SCE 2787, cefepime and cefpirome are stable against cephamycinases. Progress in antibacterial activity of parenteral cephalosporins was achieved both by structural modifications (of latamoxef or cefotaxime) and combination of Piperacillin with taxobactam. Flomoxef in comparison with latamoxef extended its spectrum to include staphylococci and increased activity against non-enterococcal streptococci 16 to 32 times. The various structural modifications of cefotaxime at position 3 of the cephalosporin ring improved the antibacterial profile of SCE 2787, cefepime and cefpirome in very much the same way (enhanced activity mainly against organisms producing chromosomal cephalosporinases, e. g.Enterobacter spp.,Serratia spp.,H. alvei, M. morganii and non-fermentative bacilli). Tazobactam protects Piperacillin against plasmidic beta-lactamases, however, this was achieved to an even higher extent by the structural modifications of aminothiazole-methoximino cephalosporins (SCE 2787, cefepime and cefpirome) and in particular of flomoxef.
Barbara E. Murray - One of the best experts on this subject based on the ideXlab platform.
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Susceptibility of β-lactamase-producing enterococci to Piperacillin with Tazobactam☆☆☆
Diagnostic Microbiology and Infectious Disease, 1993Co-Authors: Pablo C. Okhuysen, Kavindra V Singh, Barbara E. MurrayAbstract:Abstract The in vitro activity of Piperacillin with and without Tazobactam was evaluated against different inocula of 12 clinical isolates of β-lactamase-producing Enterococcus faecalis obtained from different geographic areas. Minimum inhibitory concentrations (MICs) of Piperacillin alone at ∼10 3 colony-forming units (CFU)/spot ranged from 4 to 8 and from 4 to 8 μg/ml with Piperacillin Plus Tazobactam. When ∼10 7 CFU/spot was used, MICs increased to a range of 128–1024 μg/ml Piperacillin. This inoculum effect was reversed by the addition of Tazobactam to Piperacillin at a fixed concentration of 1 μg/ml or at a ratio of 8 : 1 (Piperacillin relative to Tazobactam) with an MIC 90 of 162 μg/ml for the combination drug. In time-kill studies, four β-lactamase-producing (Bla + ) cisolates were tested and demonstrated a decrease of ≥2 log 10 with 8 or 16 μg/ml of Piperacillin in combination with 4 μg of Tazobactam, but not with Piperacillin alone. A non-β-lactamase-producing isolate was equally inhibited by Piperacillin alone and Piperacillin Plus Tazobactam. Against a Bla + isolate, the combination of Piperacillin with Tazobactam with streptomycin resulted in a synergistic effect relative to that of Piperacillin with Tazobactam; Piperacillin Plus streptomycin did not show synergism. Piperacillin in combination with Tazobactam is active against enterococci that produce β-lactamase and, in combination with an appropriate aminoglycoside, could be a viable choice for therapy of enterococci that do not have high-level resistance to all aminoglycosides.
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Susceptibility of β-lactamase-producing enterococci to Piperacillin with Tazobactam☆☆☆
Diagnostic microbiology and infectious disease, 1993Co-Authors: Pablo C. Okhuysen, Kavindra V Singh, Barbara E. MurrayAbstract:The in vitro activity of Piperacillin with and without Tazobactam was evaluated against different inocula of 12 clinical isolates of beta-lactamase-producing Enterococcus faecalis obtained from different geographic areas. Minimum inhibitory concentrations (MICs) of Piperacillin alone at approximately 10(3) colony-forming units (CFU)/spot ranged from 4 to 8 and from 4 to 8 micrograms/ml with Piperacillin Plus Tazobactam. When approximately 10(7) CFU/spot was used, MICs increased to a range of 128-1024 micrograms/ml Piperacillin. This inoculum effect was reversed by the addition of Tazobactam to Piperacillin at a fixed concentration of 1 microgram/ml or at a ratio of 8 : 1 (Piperacillin relative to Tazobactam) with an MIC90 of 16/2 micrograms/ml for the combination drug. In time-kill studies, four beta-lactamase-producing (Bla+) isolates were tested and demonstrated a decrease of > or = 2 log10 with 8 or 16 micrograms/ml of Piperacillin in combination with 4 micrograms of Tazobactam, but not with Piperacillin alone. A non-beta-lactamase-producing isolate was equally inhibited by Piperacillin alone and Piperacillin Plus Tazobactam. Against a Bla+ isolate, the combination of Piperacillin with Tazobactam with streptomycin resulted in a synergistic effect relative to that of Piperacillin with Tazobactam; Piperacillin Plus streptomycin did not show synergism. Piperacillin in combination with Tazobactam is active against enterococci that produce beta-lactamase and, in combination with an appropriate aminoglycoside, could be a viable choice for therapy of enterococci that do not have high-level resistance to all aminoglycosides.
A. Bauernfeind - One of the best experts on this subject based on the ideXlab platform.
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In vitro activity and stability against novel beta-lactamases of investigational beta-lactams (cefepime, cefpirome, flomoxef, SCE 2787 and Piperacillin Plus Tazobactam) in comparison with established compounds (cefotaxime, latamoxef and Piperacillin)
Infection, 1991Co-Authors: A. Bauernfeind, S. Schweighart, E. Eberlein, R. JungwirthAbstract:Die Perspektiven für eine Verbesserung der antiinfektiösen Therapie mit Hilfe neuer Betalaktamantibiotika (Flomoxef, SCE 2787, Cefpirom, Cefepim, Piperacillin Plus Tazobactam) im Vergleich mit Cefotaxim und Latamoxef wurden durch Vergleich ihrer in vitro Aktivitäten gegenüber 1119 Isolaten aus 83 Spezies analysiert. Escherichia coli, Klebsiella spp., Enterobacter sakazakii, Proteus spp. und Shigella spp. erwiesen sich als etwa gleich sensitiv gegenüber allen Cephalosporinen (MHK_90: 0,06 und 0,5 mg/l) während die MHK_90 für Piperacillin Plus Tazobactam zwischen 2 und 16 mg/l lagen. Enterobacter cloacae, Enterobacter aerogenes und Serratia spp. waren am empfindlichsten gegenüber SCE 2787, Cefpirom und Cefepim (MHK_90: 0,06–2 mg/l), es folgten Latamoxef, Cefotaxim, Flomoxef und Piperacillin Plus Tazobactam. Bei Citrobacter spp. Providencia spp. und Yersinia enterocolitica lagen die MHK_90 Werte zwischen 0,06 und 0,5 mg/l, Flomoxef war gegen diese Spezies 2 bis 16 mal weniger aktiv, jedoch aktiver als Piperacillin Plus Tazobactam (MHK_90: 2–8 mg/l). Gegen Morganella morganii und Hafnia alvei waren Cefepim, Cefpirom und Latamoxef die wirksamsten Substanzen (MHK_90 zwischen 0,13 und 0,5 mg/l) während Cefotaxim (MHK_90: 8 mg/l) und Piperacillin Plus Tazobactam (MHK_90: 8 bis > 64 mg/l) die niedrigste Aktivität aufwiesen. Gegen nichtfermentierende Bakterien (13 Spezies) zeigten SCE 2787, Cefepim und Cefpirom die höchste Aktivität (MHK_90: 0,5–16 mg/l). Hier waren die Oxacepheme am wenigsten wirksam. Cefepim war unter den hier verglichenen Betalaktamen das aktivste gegenüber Pseudomonas aeruginosa (MHK_90 16 mg/l). Haemophilus spp., Neisseria gonorrhoeae und Bordetella pertussis waren am empfindlichsten gegenüber Cefotaxim (MHK_90: 0,03–0,06 mg/l). Gegenüber allen grampositiven Kokken waren alle einbezogenen Substanzen deutlich stärker aktiv als Latamoxef (MHK_90 gegenüber Staphylokokken 8–64 mg/l, Streptokokken, außer Enterkokken, 4–8 mg/l). Unter den Methicillin-sensitiven Staphylokokken waren die penicillinasebildenden Staphylococcus aureus Stämme am empfindlichsten gegen Flomoxef, die Isolate der übrigen Staphylokokken Spezies waren etwa gleich sensitiv gegenüber allen Substanzen. Streptokokken (ohne Enterokokken) hatten MHK_90-Werte zwischen 0,03 und 0,5 mg/l. Streptococcus pneumoniae Isolate mit MHK-Werte für Penicillin über 1 mg/l waren zwischen 16 und 64 mal weniger empfindlich (MHK_90: 0,5 bis 4 mg/l) gegenüber anderen Betalaktamen als penicillinempfindliche Pneumokokken (MHK_90: 0,03 bis 0,13). Gegenüber Isolaten anaerober Spezies waren Flomoxef und Piperacillin Plus Tazobactam die aktivsten Substanzen. Das Oxacephem Flomoxef war die stabilste Verbindung gegenüber neuen Betalaktamasen mit erweitertem Breitsprektrum (TEM-3 bis TEM-7, SHV-2 bis SHV-5, CMY-1, CTX-M-1) gefolgt von Latamoxef. Beide Oxacephamycine werden jedoch von Cephamycinasen hydrolysiert. Weitgehend cephamycinasefest sind SCE 2787, Cefepim und Cefpirom. Somit konnten Möglichkeiten antibiotischer Therapie mithilfe parenteraler Betalaktame verbessert werden sowohl durch Derivate eingeführter Substanzen als auch durch deren Kombination mit Betalaktamaseinhibitoren (Piperacillin Plus Tazobactam): Die Latamoxef-Lücke gegenüber grampositiven Kokken ließ sich mit dem Flomoxef schließen und die Aktivität gegenüber Streptokokken um das 16- bis 32fache erhöhen. Die Cefotaxim-Derivate (SCE 2787, Cefepim, Cefpirom) verfügen bei vielen Spezies über erhöhte antibakterielle Aktivität gegenüber der Ausgangssubstanz (insbesondere gegenüber Spezies mit chromosomalen Betalaktamasen wie Enterobacter spp., Serratia spp., H. alvei, M. morganii und nichtfermentierende Bakterien). Tazobactam schützt das Piperacillin vor plasmidischen Betalaktamasen jedoch nicht in dem Ausmaß wie das durch die strukturelle Veränderung der Aminothiazolmethoximino-cephalosporinstruktur (SCE 2787, Cefepim, Cefpirom) oder insbesondere durch Flomoxef erreicht werden konnte. The therapeutic perspectives of flomoxef, SCE 2787, cefpirome, cefepime, latamoxef, cefotaxime and of Piperacillin Plus Tazobactam were comparatively evaluated by their in vitro activity against 1119 clinical isolates of 83 bacterial species. Escherichia coli, Klebsiella spp. Enterobacter sakazakii, Proteus spp. and Shigella spp. were about equally susceptible to the cephalosporins (MIC_90: 0.06 to 0.5 mg/l), while the MIC_90 for Piperacillin Plus Tazobactam was between 2 and 16 mg/l. Enterobacter cloacae, Enterobacter aerogenes and Serratia spp. were most susceptible to SCE 2787, cefpirome and cefepime (MIC_90: 0.06 to 2 mg/l) followed by latamoxef, cefotaxime, flomoxef and Piperacillin Plus Tazobactam. For Citrobacter spp., Providencia spp. and Yersinia enterocolitica MIC_90 were between 0.06 and 0.5 mg/l. Flomoxef was between 2 to 4 log_2 less active against these species but more active than Piperacillin Plus Tazobactam (MIC_90: 2 and 8 mg/l). Morganella morganii and Hafnia alvei were most susceptible to cefepime, cefpirome and latamoxef (MIC_90: 0.13 to 0.5 mg/l) while cefotaxime (MIC_90: 8 mg/l) and Piperacillin Plus Tazobactam (MIC_90: 8 and > 64 mg/l) were the least active compounds. SCE 2787, cefepime and cefpirome were the most potent beta-lactams against the majority of the 13 species of non-fermentative bacilli (NFB) investigated (MIC_90: 0.5 to 16 mg/l). The oxacephems were the least active compounds against NFB. Cefepime was the most active of the compounds included against Pseudomonas aeruginosa (MIC_90: 16 mg/l). Haemophilus spp., Neisseria gonorrhoeae and Bordetella pertussis were most susceptible to cefotaxime (MIC_90: 0.03 to 0.06 mg/l). Latamoxef had the lowest activity of all compounds against gram-positive cocci. Flomoxef was the most active compound against penicillinase producing Staphylococcus aureus and about equally active as the other betalactams against methicillin susceptible staphylococci of other staphylococcal species. Non-enterococcal streptococci had MIC_90 between 0.03 und 0.5 mg/l for all. Streptococcus pneumoniae with MICs for penicillin equal to or above 1 mg/l were between 16 and 64 times less susceptible (MIC_90: between 0.5 and 4 mg/l) than penicillin-susceptible organisms (MIC_90: between 0.03 and 0.13 mg/l). Flomoxef and Piperacillin Plus Tazobactam were the most active of the compounds against anaerobic organisms. The oxacephem flomoxef was the most stable of the compounds included against novel extended broad spectrum beta-lactamases (TEM-3 to TEM-7, SHV-2 to SHV 5, CMY-1, CTX-M-1) followed by latamoxef. However, both oxacephamycins are hydrolysed by cephamycinases while SCE 2787, cefepime and cefpirome are stable against cephamycinases. Progress in antibacterial activity of parenteral cephalosporins was achieved both by structural modifications (of latamoxef or cefotaxime) and combination of Piperacillin with taxobactam. Flomoxef in comparison with latamoxef extended its spectrum to include staphylococci and increased activity against non-enterococcal streptococci 16 to 32 times. The various structural modifications of cefotaxime at position 3 of the cephalosporin ring improved the antibacterial profile of SCE 2787, cefepime and cefpirome in very much the same way (enhanced activity mainly against organisms producing chromosomal cephalosporinases, e. g. Enterobacter spp., Serratia spp., H. alvei, M. morganii and non-fermentative bacilli). Tazobactam protects Piperacillin against plasmidic beta-lactamases, however, this was achieved to an even higher extent by the structural modifications of aminothiazole-methoximino cephalosporins (SCE 2787, cefepime and cefpirome) and in particular of flomoxef.
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In vitro activity and stability against novel beta-lactamases of investigational beta-lactams (cefepime, cefpirome, flomoxef, SCE2787 and Piperacillin Plus Tazobactam) in comparison with established compounds (cefotaxime, latamoxef and Piperacillin).
Infection, 1991Co-Authors: A. Bauernfeind, S. Schweighart, E. Eberlein, R. JungwirthAbstract:The therapeutic perspectives of flomoxef, SCE 2787, cefpirome, cefepime, latamoxef, cefotaxime and of Piperacillin Plus Tazobactam were comparatively evaluated by their in vitro activity against 1119 clinical isolates of 83 bacterial species. Escherichia coli, Klebsiella spp. Enterobacter sakazakii, Proteus spp. and Shigella spp. were about equally susceptible to the cephalosporins (MIC90: 0.06 to 0.5 mg/l), while the MIC90 for Piperacillin Plus Tazobactam was between 2 and 16 mg/l. Enterobacter cloacae, Enterobacter aerogenes and Serratia spp. were most susceptible to SCE 2787, cefpirome and cefepime (MIC90: 0.06 to 2 mg/l) followed by latamoxef, cefotaxime, flomoxef and Piperacillin Plus Tazobactam. For Citrobacter spp., Providencia spp. and Yersinia enterocolitica MIC90 were between 0.06 and 0.5 mg/l. Flomoxef was between 2 to 4 log2 less active against these species but more active than Piperacillin Plus Tazobactam (MIC90: 2 and 8 mg/l). Morganella morganii and Hafnia alvei were most susceptible to cefepime, cefpirome and latamoxef (MIC90: 0.13 to 0.5 mg/l) while cefotaxime (MIC90: 8 mg/l) and Piperacillin Plus Tazobactam (MIC90: 8 and greater than 64 mg/l) were the least active compounds. SCE 2787, cefepime and cefpirome were the most potent beta-lactams against the majority of the 13 species of non-fermentative bacilli (NFB) investigated (MIC90: 0.5 to 16 mg/l). The oxacephems were the least active compounds against NFB. Cefepime was the most active of the compounds included against Pseudomonas aeruginosa (MIC90: 16 mg/l). Haemophilus spp., Neisseria gonorrhoeae and Bordetella pertussis were most susceptible to cefotaxime (MIC90: 0.03 to 0.06 mg/l). Latamoxef had the lowest activity of all compounds against gram-positive cocci. Flomoxef was the most active compound against penicillinase producing Staphylococcus aureus and about equally active as the other betalactams against methicillin susceptible staphylococci of other staphylococcal species.(ABSTRACT TRUNCATED AT 250 WORDS)
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in vitro activity and stability against novel beta lactamases of investigational beta lactams cefepime cefpirome flomoxef sce 2787 and Piperacillin Plus Tazobactam in comparison with established compounds cefotaxime latamoxef and Piperacillin
Infection, 1991Co-Authors: A. Bauernfeind, S. Schweighart, E. Eberlein, R. JungwirthAbstract:The therapeutic perspectives of flomoxef, SCE 2787, cefpirome, cefepime, latamoxef, cefotaxime and of Piperacillin Plus Tazobactam were comparatively evaluated by theirin vitro activity against 1119 clinical isolates of 83 bacterial species.Escherichia coli, Klebsiella spp.Enterobacter sakazakii, Proteus spp. andShigella spp. were about equally susceptible to the cephalosporins (MIC90: 0.06 to 0.5 mg/l), while the MIC90 for Piperacillin Plus Tazobactam was between 2 and 16 mg/l.Enterobacter cloacae, Enterobacter aerogenes andSerratia spp. were most susceptible to SCE 2787, cefpirome and cefepime (MIC90: 0.06 to 2 mg/l) followed by latamoxef, cefotaxime, flomoxef and Piperacillin Plus Tazobactam. ForCitrobacter spp.,Providencia spp. andYersinia enterocolitica MIC90 were between 0.06 and 0.5 mg/l. Flomoxef was between 2 to 4 log2 less active against these species but more active than Piperacillin Plus Tazobactam (MIC90: 2 and 8 mg/l).Morganella morganii andHafnia alvei were most susceptible to cefepime, cefpirome and latamoxef (MIC90: 0.13 to 0.5 mg/l) while cefotaxime (MIC90: 8 mg/l) and Piperacillin Plus Tazobactam (MIC90: 8 and > 64 mg/l) were the least active compounds. SCE 2787, cefepime and cefpirome were the most potent beta-lactams against the majority of the 13 species of non-fermentative bacilli (NFB) investigated (MIC90: 0.5 to 16 mg/l). The oxacephems were the least active compounds against NFB. Cefepime was the most active of the compounds included againstPseudomonas aeruginosa (MIC90: 16 mg/l).Haemophilus spp.,Neisseria gonorrhoeae andBordetella pertussis were most susceptible to cefotaxime (MIC90: 0.03 to 0.06 mg/l). Latamoxef had the lowest activity of all compounds against gram-positive cocci. Flomoxef was the most active compound against penicillinase producingStaphylococcus aureus and about equally active as the other betalactams against methicillin susceptible staphylococci of other staphylococcal species. Non-enterococcal streptococci had MIC90 between 0.03 und 0.5 mg/l for all.Streptococcus pneumoniae with MICs for penicillin equal to or above 1 mg/l were between 16 and 64 times less susceptible (MIC90: between 0.5 and 4 mg/l) than penicillin-susceptible organisms (MIC90: between 0.03 and 0.13 mg/l). Flomoxef and Piperacillin Plus Tazobactam were the most active of the compounds against anaerobic organisms. The oxacephem flomoxef was the most stable of the compounds included against novel extended broad spectrum beta-lactamases (TEM-3 to TEM-7, SHV-2 to SHV 5, CMY-1, CTX-M-1) followed by latamoxef. However, both oxacephamycins are hydrolysed by cephamycinases while SCE 2787, cefepime and cefpirome are stable against cephamycinases. Progress in antibacterial activity of parenteral cephalosporins was achieved both by structural modifications (of latamoxef or cefotaxime) and combination of Piperacillin with taxobactam. Flomoxef in comparison with latamoxef extended its spectrum to include staphylococci and increased activity against non-enterococcal streptococci 16 to 32 times. The various structural modifications of cefotaxime at position 3 of the cephalosporin ring improved the antibacterial profile of SCE 2787, cefepime and cefpirome in very much the same way (enhanced activity mainly against organisms producing chromosomal cephalosporinases, e. g.Enterobacter spp.,Serratia spp.,H. alvei, M. morganii and non-fermentative bacilli). Tazobactam protects Piperacillin against plasmidic beta-lactamases, however, this was achieved to an even higher extent by the structural modifications of aminothiazole-methoximino cephalosporins (SCE 2787, cefepime and cefpirome) and in particular of flomoxef.
Pablo C. Okhuysen - One of the best experts on this subject based on the ideXlab platform.
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Susceptibility of β-lactamase-producing enterococci to Piperacillin with Tazobactam☆☆☆
Diagnostic Microbiology and Infectious Disease, 1993Co-Authors: Pablo C. Okhuysen, Kavindra V Singh, Barbara E. MurrayAbstract:Abstract The in vitro activity of Piperacillin with and without Tazobactam was evaluated against different inocula of 12 clinical isolates of β-lactamase-producing Enterococcus faecalis obtained from different geographic areas. Minimum inhibitory concentrations (MICs) of Piperacillin alone at ∼10 3 colony-forming units (CFU)/spot ranged from 4 to 8 and from 4 to 8 μg/ml with Piperacillin Plus Tazobactam. When ∼10 7 CFU/spot was used, MICs increased to a range of 128–1024 μg/ml Piperacillin. This inoculum effect was reversed by the addition of Tazobactam to Piperacillin at a fixed concentration of 1 μg/ml or at a ratio of 8 : 1 (Piperacillin relative to Tazobactam) with an MIC 90 of 162 μg/ml for the combination drug. In time-kill studies, four β-lactamase-producing (Bla + ) cisolates were tested and demonstrated a decrease of ≥2 log 10 with 8 or 16 μg/ml of Piperacillin in combination with 4 μg of Tazobactam, but not with Piperacillin alone. A non-β-lactamase-producing isolate was equally inhibited by Piperacillin alone and Piperacillin Plus Tazobactam. Against a Bla + isolate, the combination of Piperacillin with Tazobactam with streptomycin resulted in a synergistic effect relative to that of Piperacillin with Tazobactam; Piperacillin Plus streptomycin did not show synergism. Piperacillin in combination with Tazobactam is active against enterococci that produce β-lactamase and, in combination with an appropriate aminoglycoside, could be a viable choice for therapy of enterococci that do not have high-level resistance to all aminoglycosides.
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Susceptibility of β-lactamase-producing enterococci to Piperacillin with Tazobactam☆☆☆
Diagnostic microbiology and infectious disease, 1993Co-Authors: Pablo C. Okhuysen, Kavindra V Singh, Barbara E. MurrayAbstract:The in vitro activity of Piperacillin with and without Tazobactam was evaluated against different inocula of 12 clinical isolates of beta-lactamase-producing Enterococcus faecalis obtained from different geographic areas. Minimum inhibitory concentrations (MICs) of Piperacillin alone at approximately 10(3) colony-forming units (CFU)/spot ranged from 4 to 8 and from 4 to 8 micrograms/ml with Piperacillin Plus Tazobactam. When approximately 10(7) CFU/spot was used, MICs increased to a range of 128-1024 micrograms/ml Piperacillin. This inoculum effect was reversed by the addition of Tazobactam to Piperacillin at a fixed concentration of 1 microgram/ml or at a ratio of 8 : 1 (Piperacillin relative to Tazobactam) with an MIC90 of 16/2 micrograms/ml for the combination drug. In time-kill studies, four beta-lactamase-producing (Bla+) isolates were tested and demonstrated a decrease of > or = 2 log10 with 8 or 16 micrograms/ml of Piperacillin in combination with 4 micrograms of Tazobactam, but not with Piperacillin alone. A non-beta-lactamase-producing isolate was equally inhibited by Piperacillin alone and Piperacillin Plus Tazobactam. Against a Bla+ isolate, the combination of Piperacillin with Tazobactam with streptomycin resulted in a synergistic effect relative to that of Piperacillin with Tazobactam; Piperacillin Plus streptomycin did not show synergism. Piperacillin in combination with Tazobactam is active against enterococci that produce beta-lactamase and, in combination with an appropriate aminoglycoside, could be a viable choice for therapy of enterococci that do not have high-level resistance to all aminoglycosides.
Anurag Payasi - One of the best experts on this subject based on the ideXlab platform.
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Resistance Patterns and Prevalence of the Aminoglycoside Modifying Enzymes in Clinical Isolates of Gram Negative Pathogens
2014Co-Authors: Manu Chaudhary, Anurag PayasiAbstract:In this nationwide study we investigated the occurrence of aminoglycoside resistance patterns and prevalence of the aminoglycoside modifying enzymes (AMEs), aac(6), ant(2) and aph(3), in clinical isolates of Acinetobacter species, E. coli, Klebsiella species and Pseudomonas species isolates from various clinical specimens. A total of 319 clinical specimens recovered from urine, blood, wound, catheter tips and sputum were collected and were processed for identification of bacterial isolates in these specimens. The selected bacterial isolates were examined for susceptibility to Potentox, cefepime, amikacin, tobramycin, meropenem, gentamicin, Piperacillin Plus Tazobactam by disc diffusion method. AMEs were detected by polymerase chain reaction (PCR). A total of 255 Gram negative clinical isolates were recovered from clinical specimens that include 9.0 % of Acinetobacter species, 34.9% of Escherichia coli, 29.0% of Pseudomonas species and 27.0% of Klebsiella species. Among the 255 clinical isolates, 75.7% isolates were found to carry AMEs. The AMEs genes found were aac(6) (43.5 to 51.7%), ant(2) (17.4 to 20.2%) and aph(3) (5.6 to 10.1%) of the isolates. The most prevalent AMEs was aac(6). Our data displayed that Potentox was the most active antibacterial agent against AMEs followed by meropenem. Potentox exhibited more than 93% susceptibility to all 3 types of AMEs (aac, ant & aph) whereas meropenem response was almost 20% lesser with susceptibility ranging not more than 73.4%. Piperacillin Plus Tazobactam was found to be the least active with less than 20% susceptibility. The susceptibility of other antibacterial agents varied between 20% to
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Changing Trends of Commonly Used Intensive Care Unit Antibiotics Due to Differential Membrane Permeability in Resistant Escherichia coli Collected in EASE Programme
Journal of Microbial & Biochemical Technology, 2013Co-Authors: Manu Chaudhary, Anurag PayasiAbstract:In order to understand resistance pattern of Escherichia coli clinical isolates, the outer membrane permeability trend of different antibiotics was studied. The outer membrane permeability of Elores was compared with other commonly used intensive care unit (ICU) drugs being used in the treatment of various infections caused by resistant E. coli. A total of fifty three isolates collected under EASE programme from North Indian hospitals, fifteen extended spectrum β-lactamases (ESBL) positive clinical isolates of E. coli were included in the study. Michaelis constants (Km) and maximal rates of substrate hydrolysis (Vmax) were determined from Lineweaver-Burk plot. Permeability coefficient was determined using the method described by Zimmermann and Rosslet. Elores demonstrated the lowest Vmax/Km ratio further indicating its lower affinity (high Km 209.9 ± 17.4 μM) towards β-lactamase or more stability against β-lactamase enzyme. The other comparator drugs including penems, colistin, β-lactam and β-lactamase inhibitor combinations exhibited three to ten folds higher Vmax/Km ratio compared to Elores indicating very high affinity for β-lactamase induced degradation. Elores penetrated the outer membrane of ESBL producing resistant E. coli with permeability coefficient approximately 1.8, 2.2, 6.9, 2.5 and 2.3 times higher than imipenem Plus cilastatin, meropenem, colistin, cefoperazone Plus sulbactam, Piperacillin Plus Tazobactam, respectively. The increased penetration of the Elores leads to higher periplasmic concentration of the drug resulting in reduced MIC. Our results clearly demonstrated that Elores exhibited the highest permeability coefficient, enhanced penetration, greater stability and periplasmic concentration leading to higher susceptibility towards resistant E. coli compared to other drugs. Therefore, Elores can be considered as an empiric drug of choice for the treatment of infections caused by E. coli positive with ESBL.
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Incidence, prevalence and control of multidrug resistant (MDR) carbapenemase producing Acinetobacter baumanii in Indian intensive care units
Journal of Pharmacy Research, 2013Co-Authors: Manu Chaudhary, Anurag PayasiAbstract:Abstract Objective The objective of present study was to conduct a microbial surveillance in India to find the prevalence of carbapenemases producing genes among multidrug resistant Acinetobacter baumannii isolates isolated from various clinical specimens of ICU patients and to evaluate the comparative antimicrobial susceptibility of Elores with other drugs among these strains. Methods Phenotypic characterization of isolates was carried out by the disc diffusion method. The prevalence of carbapenemase producing gene was studied using polymerase chain reaction (PCR). Antibiotic susceptibility study was performed according to the Clinical Laboratory Standards Institute method (CLSI, 2009) in all carbapenemase producing clinical isolates. Results Among the four hundred and fifty four (454) isolates, three hundred and seventy one (371) (81.71%) isolates were found to be carbapenemase producing. Further screening of these isolates revealed that approximately 86.5% (321/371) isolates were carbapenemase positive via PCR method. The highest percentage of carbapenemase producers were confirmed via PCR in urine specimen 95.1% (137/144) followed by respiratory secretion 91.6% (11/12), blood 82.6% (95/115), pus 79.7% (55/69), and fluid 74.1% (23/31). In non-fermentor carbapenemase producing A. baumannii, none of the antibiotics yielded percentage susceptibility >40% except Elores which showed 93–96% susceptibility. Colistin appeared to be the second most active antibiotic with 21–32% susceptibility followed by tigecycline (21–25%), doripenem (9–14%) and each of imipenem and meropenem (1–4%). None of the isolates was found to be susceptible to Piperacillin Plus Tazobactam. Interestingly, penems (doripenem, imipenem and meropenem) exhibited 71–91% resistant and 6.8–14.3% intermediate response to carbapenemase producing A. baumannii isolates. Conclusion Results of the present study revealed that Elores was the most active amongst commonly used antibiotics in ICU settings, which showed 93–96% susceptibility, therefore can be a potent antibacterial option for the treatment of infections caused by carbapenemase producing A. baumannii .
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Elores : A New Antibiotic Adjuvant Entity Active Against Metallo-β-Lactamases Producing Organisms
2013Co-Authors: Manu Chaudhary, Anurag PayasiAbstract:The aim of the present study was to investigate the prevalence of New Delhi metallo-β-lactamase (NDM-1) in multi-drug resistant Enterobacteriaceae particularly Escherichia coli and Klebsiella pneumoniae and in nonfermenting gram-negative bacilli (Acinetobacter baumannii and Pseudomonas aeruginosa) in India and compared the antibacterial activity of Elores with other βlactam antibiotics against these NDM-1 producing isolates. Phenotypic characterization of the isolates was done using imipenem and imipenem+EDTA (ethylenediaminetetra acetic acid) disc diffusion method. The prevalence of NDM-1 among these isolates was studied using polymerase chain reaction (PCR). Antibiotic susceptibility study was performed according to the Clinical Laboratory Standards Institute method (CLSI). Out of the five hundred forty one isolates, four hundred sixty four isolates (85.7 %) were found to be carbapenem resistant. Further screening of these isolates revealed approximately 81.7 % (379/464) isolates were found to be NDM-1 positive through PCR method. Elores appeared to be most active antibacterial agents with 95.0% susceptibility to NDM-1 positive K. pneumoniae followed by A. baumannii (94.0 %), E. coli (93.5%) and P. aeruginosa (92.8 %), however, it showed 1 to 2% resistant and 3 to 6 % intermediate response to these isolates. Among the penems (imipenem+cilastatin, doripenem and meropenem), imipenem Plus cilastatin showed 100 % resistant to A. baumannii, P. aeruginosa and K. pneumoniae against NDM-1 producing isolates whereas doripenem exhibited 5.5% susceptibility and 79.6% resistant to E. coli followed by A. baumannii (4.5% susceptibility, 86.5% resistance), K. pneumoniae (1.6% susceptibility, 91.6% resistance) and P. aeruginosa (1.2% susceptibility, 95.2 % resistance) while meropenem showed 1 to 2 % susceptibility, 88 to 97% resistance and 1 to 8 % intermediate response against E. coli, K. pneumoniae, A. baumannii and P. aeruginosa. Piperacillin Plus Tazobactam demonstrated 88 to 93 % resistance, and 6 to 7 % intermediate response and only 1 to 3 % susceptibility response. In conclusion, Elores was the most active which showed 92 to 95 % susceptibility therefore can be a potent antibacterial agent for the treatment of infections caused by carbapenemase producing A. baumannii.
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Prospective Study for Antimicrobial Susceptibility of Escherichia coli Isolated from Various Clinical Specimens in India
Journal of Microbial & Biochemical Technology, 2012Co-Authors: Manu Chaudhary, Anurag PayasiAbstract:The aim of the present work was to study the prevalence of Extended-spectrum β-lactamases (ESBLs) and Metallo-β-lactamases (MβLs) among 464 E. coli clinical isolates obtained from various clinical specimens; and to study the susceptibility of various drugs against E. coli isolates. Phenotypic characterization and susceptibility studies were performed according to the methods described in Clinical and Laboratory Standards Institute guidelines (CLSI, 2010). The prevalence of ESBLs and MβLs was analyzed with Polymerase Chain Reaction (PCR), using the previously reported primers. Among the four hundred sixty four isolates, 186 (40.08%) isolates were ESBLs positive, 75 (16.16%) isolates were MβLs positive, and 80 (17.24%) were both ESBLs and MβLs positive. The remaining 123 (26.50%) were non ESBLs and MβLs. TEM-types ESBLs (blaTEM-1, blaTEM-2, and blaTEM-50) were found in approximately 57% isolates. The prevalence of SHV-types, CTX-M-types and OXA-type was 29.03, 11.82 and 2.15%, respectively. Among the MβLs, the frequency of distribution of NDM-1, IMP-1, VIM-1 and KPC-types was 37.39, 21.33, 18.66, and 22.66%, respectively. In general, 92.6% E. coli isolates were susceptible to ceftriaxone Plus EDTA Plus sulbactam (CSE1034), followed by meropenem (74.4%), imipenem (71.2%), Piperacillin Plus Tazobactam (52.1%), cefoperazone Plus sulbactam (46.0%) and amoxycillin Plus clavulanic acid (23.6%). Similarly, amoxycillin Plus clavulanic acid showed the highest percentage of resistance (72.8%), followed by cefoperazone Plus sulbactam (43.6%), Piperacillin Plus Tazobactam (39.3%), imipenem (23.3%), meropenem (20.3%) and ceftriaxone Plus EDTA Plus sulbactam (CSE1034) (2.5%). Results of the present study revealed that most of the clinical isolates were susceptible to ceftriaxone Plus EDTA Plus sulbactam (CSE1034), and can be a potent antibacterial agent for the treatment of severe bacterial infections caused by E. coli.